(a) Field of the Invention
The present invention relates to a composition for prevention or treatment of neurodegenerative disease comprising longan arillus extract, or combined extract comprising the same, more particularly to a pharmaceutical composition or a food composition for prevention or treatment of neurodegenerative disease comprising the extract as an active ingredient.
(b) Description of the Related Art
A neurodegenerative disease primarily represented by Parkinson's Disease is characterized by dopaminergic neuron death in substantia nigra pars compacta. The decrease of dopamine, a neurotransmitter in striatum adversely affects the balance of neurotransmission system, thus showing representative symptoms of Parkinson's Disease including tremor, rigidity, bradykinesia, and postural instability, etc.
However, the pathological cause of neurodegenerative disease such as Parkinson's Disease has not been clarified. It has been limitedly hypothesized that loss of dopaminergic neurons may be caused by genetic factors or external toxicity, etc., and recent studies have reported that cerebral arteriosclerosis, carbon monoxide-poisoning, drugs, metabolic diseases caused by hypoparathyroidism, and traumatic encephalitis sequelae may have some connections therewith.
Although effective therapies for neurodegenerative disease have been scarcely developed until 1970's, supplementing a dopamine decrease in brain tissue using dopamine precursor L-dopa, or a therapy using dopamine receptor agonist including anticholinergic drug, for example Eldepryl has been currently known. However, most of these drugs focus on only controlling symptoms rather than treating underlying cause, and a long term administration of these drugs may cause side-effects. For example, since anticholinergic drugs may cause abnormalities in autonomic nervous system or mental function, there is a limit in continuously administering to an elderly patient. In addition, a long term use of L-dopa medication shows a gradual decrease in its effectiveness and also causes side effects, e.g., abnormal movements such as body twist and involuntary movement of hands and feet. Surgical therapies such as a nerve stimulation using high frequency, i.e., radiofrequency ablation or deep brain stimulation, etc. have been performed, but it may require an invasive surgical procedure and high costs.
Accordingly, although the development of symptomatic treatment for improving clinical symptoms is important in the treatment of neurodegenerative disease such as Parkinson's Disease, the development of causative treatment for preventing death of dopaminergic neurons in substantia nigra, which is a direct cause of Parkinson's Disease, is urgently required.
According to recent studies on the cause of neurodegenerative disease such as Parkinson's Disease, a protein called alpha-synuclein has been found in the brain of a patient suffering from Parkinson's Disease in an abnormally folded form. The accumulation of alpha-synuclein in cells, leading to destruction of neurons is known to be one of characteristics of Parkinson's Disease. Thus, studies on the method of dissolving or preventing aggregation of such abnormal proteins have attracted much attention as a novel therapy for preventing or delaying the progression of Parkinson's Disease. (Ryu, J. et al. Quality evolution and components of Euphoria longana. Kor. J. Pharmacogn. 33; 191˜193, 2002)
Meanwhile, Ubiquitin-proteasome system (UPS) is a representative proteolysis mechanism occurring in human body, and it is known that in many patients with neurodegenerative disease, such function is attenuated and thus accumulation of modified proteins cannot be controlled (Olanow C. W, McNaught K. S. Ubiquitin-proteasome system and Parkinson's disease. Mov. Disord. 2006; 21:1806-1823). In addition to UPS, an important proteolysis mechanism includes Autophagy-lysosomal pathway (ALP), which has been recently studied as an important target for treatment of neurodegenerative diseases (Bandhyopadhyay U, Cuervo A M. Chaperone-mediated autophagy in aging and neurodegeneration: lessons from alpha-synuclein. Exp Gerontol. 2007; 42:120-8). Specifically, if the function of UPS becomes abnormal and decomposition of lysosome is blocked, another proteolysis pathway called autophagy is activated as a way of compensation. In this mechanism, abnormal proteins such as alpha-synuclein are decomposed and proteins are accumulated in brain neurons to prevent cell damage (Martinez-Vicente M. Cuervo A. M, Autophagy and neurodegeneration: when the cleaning crew goes on strike. Lancet Neurol. 2007; 6:352-361, Ravikumar B, Duden R, Rubinsztein D. C. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol. Genet. 2002; 11:1107-1117). Therefore, it is important to develop a therapy through ALP, i.e. autophagy in patients with neurodegenerative disease having abnormal UPS function.